Combination Chemotherapy, Donor Stem Cell Transplant, Tacrolimus, Mycophenolate Mofetil, and Cyclophosphamide in Treating Patients With Hematologic Cancer
NCT ID: NCT00782379
Last Updated: 2013-11-21
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
20 participants
INTERVENTIONAL
2008-10-31
2012-04-30
Brief Summary
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PURPOSE: This phase II trial is studying how well combination chemotherapy works when given together with a donor stem cell transplant, followed by tacrolimus, mycophenolate mofetil, and high-dose cyclophosphamide, in treating patients with high-risk hematologic cancer.
Detailed Description
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Primary
* To estimate the incidence of graft rejection and severe graft-versus-host disease after myeloablative HLA-mismatched peripheral blood stem cell transplantation (PBSCT) from first-degree relatives in patients with high-risk hematologic malignancies.
Secondary
* To estimate overall survival, relapse, non-relapse mortality, and event-free survival in these patients.
* To characterize additional hematologic and non-hematologic toxicities of myeloablative haploidentical PBSCT.
* To characterize donor hematopoietic chimerism in peripheral blood stem cells after PBSCT.
OUTLINE:
* Preparative regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV over 1-2 hours on days -3 and -2.
* Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo infusion of unmanipulated peripheral blood stem cells on day 0.
* Post-transplant regimen: Patients receive high-dose cyclophosphamide IV over 1-2 hours on days 3 and 4, tacrolimus IV over 24 hours or orally twice daily on days 5-180, and oral mycophenolate mofetil 3 times daily on days 5-34 followed by a taper to day 90. Treatment continues in the absence of disease progression or clinically significant graft-vs-host disease.
After completion of PBSCT, patients are followed periodically for 1 year.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Myeloablative Haploidentical Transplant
All patients will receive treatment using Fludarabine, Busulfan and Cyclophosphamide prior to receiving a haploidentical transplant followed by post-transplant cyclosphosphamide.
busulfan
110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)
cyclophosphamide
14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).
fludarabine phosphate
30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)
mycophenolate mofetil
15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.
tacrolimus
0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.
allogeneic hematopoietic stem cell transplantation
Patients to received unmanipulated PBSCs on Day 0
peripheral blood stem cell transplantation
patients to receive unmanipulated PBSCs on day 0
Interventions
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busulfan
110 mg/m2 infused over 3 hours once daily on 4 consecutive days (Days -7, -6, -5, -4)
cyclophosphamide
14.5 mg/kg infused over 1-2 hours once daily on 2 consecutive days (days -3,-2).
fludarabine phosphate
30mg/m2 infused over 30 minutes once daily on three consecutive days (days -5, -4, -3)
mycophenolate mofetil
15 mg/kg po three times a daily with a maximum dose of 3gm/day starting D+5. To be discontinued on Day +35 in the absence of clinically significant GVHD.
tacrolimus
0.03 mg/kg/day infuse over 24 hours starting on day +5 (adjusted to maintain trough level of 5-15 ng/ml). Switch to oral (twice daily divided dose) on day +21 or when able to tolerate PO. Discontinue on day +180 in the absence of clinically significant GVHD.
allogeneic hematopoietic stem cell transplantation
Patients to received unmanipulated PBSCs on Day 0
peripheral blood stem cell transplantation
patients to receive unmanipulated PBSCs on day 0
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Diagnosis of one of the following high-risk hematologic malignancies:
* Chronic myelogenous leukemia meeting one of the following criteria:
* Disease in chronic phase and resistant to available tyrosine kinase inhibitors
* Disease in accelerated phase
* Disease with blast crisis that has entered into a second chronic phase after induction chemotherapy
* Acute myelogenous leukemia meeting the following criteria:
* Marrow blasts \< 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
* Must meet one of the following criteria:
* Disease in second or subsequent complete remission
* Primary induction chemotherapy failure with disease subsequently entering complete remission
* Disease in first complete remission with poor-risk cytogenetics or arising from preceding hematological disease
* Myelodysplastic syndrome meeting at least one of the following criteria:
* Treatment-related
* Monosomy 7 or complex cytogenetics
* International prognostic scoring system score ≥ 1.5
* Chronic myelomonocytic leukemia
* Acute lymphocytic leukemia or lymphoblastic lymphoma meeting the following criteria:
* Marrow blasts \< 5% but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
* Must meet one of the following criteria:
* Disease in second or subsequent complete remission
* Acute lymphocytic leukemia with poor-risk karyotype \[e.g., t(9;22) or bcr-abl fusion, t(4;11), or other MLL translocation\] and in first complete remission
* Chronic lymphocytic leukemia or prolymphocytic leukemia meeting both of the following criteria:
* Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
* In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy)
* Hodgkin or non-Hodgkin lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse disease) meeting the following criteria:
* Previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
* In the opinion of the transplant physician, unlikely to benefit from reduced intensity transplantation due to the presence of one or more high-risk features (i.e., bulky tumor masses, B symptoms, and/or inadequate response to salvage chemotherapy) NOTE: A new classification scheme for adult non-Hodgkin lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
* No available matched related or unrelated donor OR a matched related or unrelated donor will not be available in the time frame necessary to perform a transplant
* Availability of a first-degree relative (parent, child, sibling) matched at 3/6-5/6 loci (HLA-A, -B, -DR)
* Donor must be willing to donate mobilized peripheral blood stem cells
* No positive HLA crossmatch in the host-vs-graft direction or high titer donor-specific antibodies
PATIENT CHARACTERISTICS:
* Karnofsky performance status 70-100%
* Bilirubin \< 2 mg/dL (unless due to hemolysis, Gilbert syndrome, or primary malignancy)
* Creatinine \< 2 mg/dL OR creatinine clearance ≥ 40 mL/min
* Not pregnant
* Fertile patients must use effective contraception
* LVEF (Left ventriculr ejection fraction) ≥ 45%
* FEV\_1 and forced vital capacity ≥ 50% predicted
* No HIV positivity
* No debilitating medical or psychiatric illness that would preclude giving informed consent or receiving optimal treatment and follow-up
PRIOR CONCURRENT THERAPY:
* See Disease Characteristics
* No immunosuppressive agents ≤ 24 hours after completion of post-transplant cyclophosphamide (including steroids as antiemetics)
18 Years
60 Years
ALL
No
Sponsors
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Northside Hospital, Inc.
OTHER
Responsible Party
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Principal Investigators
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Scott R. Solomon, MD
Role: PRINCIPAL_INVESTIGATOR
Blood and Marrow Transplant Group of Georgia
H. Kent Holland, MD
Role: PRINCIPAL_INVESTIGATOR
Blood and Marrow Transplant Group of Georgia
Asad Bashey, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Blood and Marrow Transplant Group of Georgia
Lawrence E. Morris, MD
Role: PRINCIPAL_INVESTIGATOR
Blood and Marrow Transplant Group of Georgia
Locations
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Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States
Countries
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Other Identifiers
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BMTGG-NSH-864
Identifier Type: -
Identifier Source: secondary_id
CDR0000617648
Identifier Type: -
Identifier Source: org_study_id